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Cultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry ( Fragaria   ×   ananassa ) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry. Chromosome-scale assembly for the cultivated octoploid strawberry ( Fragaria × ananassa ) uncovers the origin and evolutionary processes that shaped this complex allopolyploid, providing a useful resource for genome-wide analyses and molecular breeding.

In an empirical analysis of transposable element (TE) abundance within natural populations of Mimulus guttatus and Drosophila melanogaster , we found a surprisingly high variance of TE count (e.g., variance-to-mean ratio on the order of 10 to 300). To obtain insight regarding the evolutionary genetic mechanisms that underlie the overdispersed population distributions of TE abundance, we developed a mathematical model of TE population genetics that includes the dynamics of element proliferation and purifying selection on TE load. The modeling approach begins with a master equation for a birth-death process and extends the predictions of the classical theory of TE dynamics in several ways. In particular, moment-based analyses of population distributions of TE load reveal that overdispersion is likely to arise via copy-and-paste proliferation dynamics, especially when the elementary processes of proliferation and excision are approximately balanced. Parameter studies and analytic work confirm this result and further suggest that overdispersed population distributions of TE abundance are probably not a consequence of purifying selection on total element load.

We sequenced the transcriptome of brainstem interneurons in the specialized respiratory rhythmogenic site dubbed preBötzinger Complex (preBötC) from newborn mice. To distinguish molecular characteristics of the core oscillator we compared preBötC neurons derived from Dbx1-expressing progenitors that are respiratory rhythmogenic to neighbouring non-Dbx1-derived neurons, which support other respiratory and non-respiratory functions. Results in three categories are particularly salient. First, Dbx1 preBötC neurons express κ-opioid receptors in addition to μ-opioid receptors that heretofore have been associated with opiate respiratory depression, which may have clinical applications. Second, Dbx1 preBötC neurons express the hypoxia-inducible transcription factor Hif1a at levels three-times higher than non-Dbx1 neurons, which links core rhythmogenic microcircuits to O 2 -related chemosensation for the first time. Third, we detected a suite of transcription factors including Hoxa4 whose expression pattern may define the rostral preBötC border, Pbx3 that may influence ipsilateral connectivity, and Pax8 that may pertain to a ventrally-derived subset of Dbx1 preBötC neurons. These data establish the transcriptomic signature of the core respiratory oscillator at a perinatal stage of development.

Background Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes gives clues as to whether any of these evolutionary processes have occurred. Results We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two conditions (e.g., tissues). We demonstrate an application of this test by comparing homeolog expression patterns of 1448 homeologous gene pairs using RNA-seq data generated from leaves and petals of an allotetraploid monkeyflower ( Mimulus luteus ). We assess the sensitivity of this test to different levels of homeolog expression bias and compare the method to several alternatives. Conclusions The likelihood ratio test derived here is a direct, transparent, and easily implemented method for detecting changes in homeolog expression bias that outperforms alternative approaches. While our method was derived with homeolog analysis in mind, this method can be used to analyze changes in the ratio of expression levels between any two genes in any two conditions.

With the availability of complete genome sequence for Drosophila melanogaster , one of the next strategic goals for fly researchers is a complete gene knockout collection. The P -element transposon 1 , the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum 2 . It has been estimated that 87% saturation of the ∼13,500-gene complement of D. melanogaster 3 might require generating and analyzing up to 150,000 insertions 2 . We describe specific improvements to the lepidopteran transposon piggyBac 4 and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5′ regulatory sequences.

Effects of renin-angiotensin system blockade on renal angiotensin-(1-7) forming enzymes and receptors. Angiotensin-converting enzyme (ACE)2, a homologue of ACE, which is insensitive to ACE inhibitors and forms angiotensin-(1-7) [Ang-(1-7)] from angiotensin II (Ang II) with high efficiency was investigated in response to chronic blockade with lisinopril, losartan, and both drugs combined. Thirty-six adult Lewis rats were assigned to receive these medications in their drinking water for 2 weeks while their arterial pressure, water intake, and urine volume were recorded throughout the study. Measures of renal excretory variables included assessing excretion rates of angiotensin I (Ang I), Ang II and Ang-(1-7) while blood collected at the completion of the study was used for measures of plasma angiotensin concentrations. Samples from renal cortex were assayed for renin, angiotensinogen (Aogen), neprilysin, angiotensin types 1 and 2 (AT1 and AT2) and mas receptor mRNAs by semiquantitative reverse transcriptase (RT) real-time polymerase chain reaction (PCR). ACE2 activity was determined as the rate of Ang II conversion into Ang-(1-7). Comparable blood pressure reductions were obtained in rats medicated with either lisinopril or losartan, whereas both drugs produced a greater decrease in arterial pressure. Polyuria was recorded in all three forms of treatment associated with reduced osmolality but no changes in creatinine excretion. Lisinopril augmented plasma levels and urinary excretion rates of Ang I and Ang-(1-7), while plasma Ang II was reduced with no effect on urinary Ang II. Losartan produced similar changes in plasma and urinary Ang-(1-7) but increased plasma Ang II without changing urinary Ang II excretion. Combination therapy mimicked the effects obtained with lisinopril on plasma and urinary Ang I and Ang-(1-7) levels. Renal cortex Aogen mRNA increased in rats medicated with either lisinopril or the combination, whereas all three treatments produced a robust increase in renal renin mRNA. In contrast, ACE, ACE2, neprilysin, AT1, and mas receptor mRNAs remained unchanged with all three treatments. Renal cortex ACE2 activity was significantly augmented in rats medicated with lisinopril or losartan but not changed in those given the combination. Our data revealed a role for ACE2 in Ang-(1-7) formation from Ang II in the kidney of normotensive rats as primarily reflected by the increased ACE2 activity measured in renal membranes from the kidney of rats given either lisinopril or losartan. The data further indicate that increased levels of Ang-(1-7) in the urine of animals after ACE inhibition or AT1 receptor blockade reflect an intrarenal formation of the heptapeptide.

An Ohio family with roots in the South, the Ewings influenced the course of the Midwest for more than fifty years. Patriarch Thomas Ewing, a former Whig senator and cabinet member who made his fortune as a real estate lawyer, raised four major players in the nation's history—including William Tecumseh \"Cump\" Sherman, taken into the family as a nine-year-old, who went on to marry his foster sister Ellen. Ronald D. Smith now tells of this extraordinary clan that played a role on the national stage through the illustrious career of one of its sons. In Thomas Ewing Jr.: Frontier Lawyer and Civil War General, Smith introduces us to the Ewing family, little known except among scholars of Sherman, to show that Tom Jr. had a remarkable career of his own: first as a real estate lawyer, judge, soldier, and speculator in Kansas, then as a key figure in national politics. Smith takes readers back to Bleeding Kansas, with its border ruffians and land speculators, reconstructing the rough-and-tumble of its courtrooms to demonstrate that its turmoil was as much about claim-jumping as about slavery. He describes the seat-of-the-pants law practice in which Ewing worked with his brothers Hugh and Charlie and foster brother Cump. He then tells how Tom came to national prominence in the fight over the proslavery Lecompton Constitution, was instrumental in starting up the Union Pacific Railroad, and became the first chief justice of the Kansas Supreme Court. Ewing obtained a commission in the Union Army—as did his brothers—and raised a regiment that saw significant action in Arkansas and Missouri. After William Quantrill's raid on Lawrence, Kansas, he issued the dramatic General Order No. 11 that expelled residents from sections of western Missouri. Then this confidant of Abraham Lincoln's went on to courageously defend three of the assassination conspirators—including the disingenuous Samuel Mudd—and lobbied the key vote to block the impeachment of Andrew Johnson. Smith examines Ewing's life in meticulous detail, mining family correspondence for informative quotes and digging deep into legal records to portray lawmaking on the frontier. And while Sherman has been the focus of most previous work on the Ewings, this book fills the gaps in an interlocking family of remarkable people—one that helped shape a nation's development in its courtrooms and business suites. Thomas Ewing Jr.: Frontier Lawyer and Civil War General retells a chapter of Kansas history and opens up a panoramic view of antebellum America, the Civil War, Reconstruction, and the Gilded Age.

Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure. This double-blind trial was undertaken in 255 sites in 30 countries. 3846 patients with heart failure of New York Heart Association class II–IV, left-ventricular ejection fraction 40% or less, and intolerance to angiotensin-converting-enzyme (ACE) inhibitors were randomly assigned to losartan 150 mg (n=1927) or 50 mg daily (n=1919). Allocation was by block randomisation stratified by centre and presence or absence of β-blocker therapy, and all patients and investigators were masked to assignment. The primary endpoint was death or admission for heart failure. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00090259. Six patients in each group were excluded because of poor data quality. With 4·7-year median follow-up in each group (IQR 3·7–5·5 for losartan 150 mg; 3·4–5·5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0·90, 95% CI 0·82–0·99; p=0·027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 mg group died (HR 0·94, 95% CI 0·84–1·04; p=0·24), and 450 versus 503 patients were admitted for heart failure (0·87, 0·76–0·98; p=0·025). Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group. Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 mg daily. These findings show the value of up-titrating ARB doses to confer clinical benefit. Merck (USA).